The objective of this study is to determine the pathogenesis of human and canine cyclic hematopoiesis. In the Knoxville-Maryville area we have a family of four generations in which cyclic neutropenia is present in at least four and possibly five members. In addition, at the University of Tennessee Memorial Research Center, we have a colony of grey collie dogs which have cyclic hematopoiesis. The study will determine if fluctuations of blood elements, other than neutrophils occur. In vitro labeling of peripheral blood with 3HTdR will be carried out, and urine will be tested for its ability to stimulate hematopoiesis in vivo and in vitro. In the dogs, leukocyte releasing and stimulating factors will be determined. A search will be made for hematopoietic stimulators and inhibitors of both short-range and long-range varieties. One such factor must be present in dogs, since on exposure to a constant environment of hypoxia, secondary peaks of erythropoietin develop. The proliferative capabilities and kinetics of bone marrow maturation for both human patients and the dogs will be assessed by use of diffusion chambers. The responsivity to exogenous agents known to normally stimulate erythropoiesis will be determined for each day of the cycle in the grey collies. The molecular mechanism of agents such as erythropoietin on bone marrow function will be under study. Finally, the agents, present in these patients and dogs which stimulate or inhibit hematopoiesis, will be characterized.